The present invention relates to a method for the use of branched-chain amino acids to improve ventilation during sleep. More specifically, the present invention relates to a method for treating sleep related ventilation problems, such as apnea.
Sleep apnea is recognized as a serious and often life threatening abnormality of the breathing pattern. See, Kales, et al, Sleep Disorders: Sleep Apneas and Narcolepsy, Ann. Intern. Med., 106:434-443, 1987. The morbidity of sleep apnea is due to a decrease oxygenation of the arterial blood and carbon dioxide retention secondarily to alveolar hypoventilation.
The condition of sleep apnea has been defined as the cessation of breathing for at least 10 seconds, that occurs at least 30 times during a 7 hour period of sleep. This definition, however, is based on sleep laboratory studies and accordingly, is not clinically applicable. Instead, arterial oxygen desaturation during sleep is the critical factor in determining sleep apnea. See, Block, et al, Sleep Apnea, Hypopnea and Oxygen Desaturation in Normal Subjects, New England Journal of Medicine, 300:513-517, 1979.
The sleep apnea syndrome has been observed as a primary disease in otherwise healthy subjects. Apneas can be divided into three sub-groups: central; obstructive; and mixed. Abnormal respiratory control is believed to be involved in all types of sleep apneas. Apneic breathing patterns during sleep occur also in association with certain other conditions, such as: morbid obesity; coronary disease; and congestive heart failure. See, Walse, et al, Upper Airway Obstruction in Obese Patients With Sleep Disturbances and Somnolence, Ann. Intern. Med. 76: 185-192, 1972; DeOlazabal, et al, Disordered Breathing and Hypoxia During Sleep in Coronary Artery Disease, Chest, 82:548-552, 1982; and Dark, et al, Breathing Pattern Abnormalities and Arterial Desaturation During Sleep in the Congestive Heart Failure Syndrome, Improvement Following Medical Therapy, Chest, 91:833-836, 1987. Patients recovering from anesthesia also frequently exhibit apneic breathing patterns.
Most patients with sleep apnea snore heavily and many exhibit severe oxygen desaturation. Oxygen desaturation during sleep may be associated with pulmonary and systematic hypertension and cardiac arrhythmias. Tilkian, et al, Sleep-Induced Apnea Syndrome, Prevelance of Cardiac Arrhythmias and Their Reversal After Tracheostomy. Am.J.Med. 63(3):348-358, 1976; and Tilkian, et al, Hemodynamics in Sleep-Induced Apnea, Am. Intern. Med. 85(6):714-719, 1977.
The typical management of sleep apnea syndrome is to relieve upper air obstruction and to also stimulate respiratory activity. Typically, pharmacologic techniques are utilized to achieve these goals. However, drug therapy alone is not usually effective in relieving sleep apneas. Moreover, such drug therapies are often associated with adverse side effects.
One drug that is used is Medroxyprogesterone acetate (MPA). MPA has been found to be a moderate, sustained ventilatory stimulant in man. MPA reduces sleep apnea in less than half of all patients. Strohl, et al, Progresterone Administration and Progressive Sleep Apneas, J. A. M. A., 245:1230-1232, 1981. But, MPA causes impotence in men and therefore the desirability and use of this drug is limited.
Another drug, protiptyline has been found to improve sleep apnea in some patients. This drug, however, is associated with such serious side effects such as: constipation; urinary retention; ataxia; and confusion. Brownell, et al, Protiptyline in Obstructive Sleep Apnea, New England Journal of Medicine, 307:1037-1042, 1982.
Accordingly, although pharmacologic interventions can be, in some cases, effective in decreasing the frequency and duration of sleep apneas, and the extent of oxygen desaturation in patients, the usefulness of such drug therapy is limited due to the adverse side effects of such drugs. Therefore, there is a need for an improved therapy for treating patients with sleep apnea.